Sunitinib malate and figitumumab in solitary fibrous tumor: Patterns and molecular bases of tumor response

Silvia Stacchiotti, Tiziana Negri, Elena Palassini, Elena Conca, Alessandro Gronchi, Carlo Morosi, Antonella Messina, Ugo Pastorino, Marco A. Pierotti, Paolo G. Casali, Silvana Pilotti

Research output: Contribution to journalArticle

Abstract

Antiangiogenic treatment activity has been reported in solitary fibrous tumor (SFT), a rare and little chemosensitive sarcoma. We explored the activity of sunitinib malate (SM) in SFT and studied receptor tyrosine kinase (RTK) activation profile. Eleven patients with progressive metastatic SFT resistant to chemotherapy were treated with continuous-dosing 37.5 mg/d SM on a named-use basis. One of them also received the insulin-like growth factor I receptor (IGFIR) inhibitor figitumumab after developing secondary resistance to SM. Besides, biochemical, molecular, and fluorescence in situ hybridization analyses were done in eight naïve SFTs whose cryopreserved material was available to clarify RTK upstream and downstream signaling. In two cases treated with SM and belonging to the naïve series, both pretreatment and posttreatment samples were available. Ten patients were evaluable for response to SM. The best response according to the Choi criteria was six partial response (all with Response Evaluation Criteria in Solid Tumors stable disease), one stable disease, and three progressive disease. Responses lasted >6 months in five patients. The eight naïve samples showed high expression/phosphorylation of PDGFRB, epidermal growth factor receptor, and IGFIR/IR, in the presence of their cognate ligands. Downstream pathways revealed expression/activation of Akt, extracellular signal-regulated kinase 1-2 and, closely related to SFT subtypes, of S6 and 4E-BP1. In two patients, whose pretreatment and posttreatment clinical and molecular status were available, biochemical data confirmed the activity of SM, although they also suggested a possible time-dependent shift of dominant RTK from PDGFRB to IGFIR/insulin receptor. A Response Evaluation Criteria in Solid Tumors partial response to figitumumab corroborated these findings. SM has antitumor activity in SFT, possibly through a PDGFRB-mediated mechanism, but treatments with IGFIR/insulin receptor and possibly epidermal growth factor receptor inhibitors are worth testing.

Original languageEnglish
Pages (from-to)1286-1297
Number of pages12
JournalMolecular Cancer Therapeutics
Volume9
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Solitary Fibrous Tumors
IGF Type 1 Receptor
Platelet-Derived Growth Factor beta Receptor
Receptor Protein-Tyrosine Kinases
Neoplasms
Insulin Receptor
Epidermal Growth Factor Receptor
S 6
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
figitumumab
sunitinib
Fluorescence In Situ Hybridization
Sarcoma
Phosphorylation
Ligands
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Sunitinib malate and figitumumab in solitary fibrous tumor: Patterns and molecular bases of tumor response",
abstract = "Antiangiogenic treatment activity has been reported in solitary fibrous tumor (SFT), a rare and little chemosensitive sarcoma. We explored the activity of sunitinib malate (SM) in SFT and studied receptor tyrosine kinase (RTK) activation profile. Eleven patients with progressive metastatic SFT resistant to chemotherapy were treated with continuous-dosing 37.5 mg/d SM on a named-use basis. One of them also received the insulin-like growth factor I receptor (IGFIR) inhibitor figitumumab after developing secondary resistance to SM. Besides, biochemical, molecular, and fluorescence in situ hybridization analyses were done in eight na{\"i}ve SFTs whose cryopreserved material was available to clarify RTK upstream and downstream signaling. In two cases treated with SM and belonging to the na{\"i}ve series, both pretreatment and posttreatment samples were available. Ten patients were evaluable for response to SM. The best response according to the Choi criteria was six partial response (all with Response Evaluation Criteria in Solid Tumors stable disease), one stable disease, and three progressive disease. Responses lasted >6 months in five patients. The eight na{\"i}ve samples showed high expression/phosphorylation of PDGFRB, epidermal growth factor receptor, and IGFIR/IR, in the presence of their cognate ligands. Downstream pathways revealed expression/activation of Akt, extracellular signal-regulated kinase 1-2 and, closely related to SFT subtypes, of S6 and 4E-BP1. In two patients, whose pretreatment and posttreatment clinical and molecular status were available, biochemical data confirmed the activity of SM, although they also suggested a possible time-dependent shift of dominant RTK from PDGFRB to IGFIR/insulin receptor. A Response Evaluation Criteria in Solid Tumors partial response to figitumumab corroborated these findings. SM has antitumor activity in SFT, possibly through a PDGFRB-mediated mechanism, but treatments with IGFIR/insulin receptor and possibly epidermal growth factor receptor inhibitors are worth testing.",
author = "Silvia Stacchiotti and Tiziana Negri and Elena Palassini and Elena Conca and Alessandro Gronchi and Carlo Morosi and Antonella Messina and Ugo Pastorino and Pierotti, {Marco A.} and Casali, {Paolo G.} and Silvana Pilotti",
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T2 - Patterns and molecular bases of tumor response

AU - Stacchiotti, Silvia

AU - Negri, Tiziana

AU - Palassini, Elena

AU - Conca, Elena

AU - Gronchi, Alessandro

AU - Morosi, Carlo

AU - Messina, Antonella

AU - Pastorino, Ugo

AU - Pierotti, Marco A.

AU - Casali, Paolo G.

AU - Pilotti, Silvana

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